INTRODUCTION: Achalasia is a primary esophageal motility disorder with heterogeneous manometric subtypes and prognosis, characterized by degeneration of the esophageal myenteric plexus, and reduction in interstitial cells of Cajal (ICCs). This study aimed to explore the histopathologic characteristics of lower esophageal sphincter (LES) muscle from patients with achalasia with different subtypes and different prognosis. METHODS: We examined specimens of LES muscle from 122 patients with achalasia who underwent peroral endoscopic myotomy and from 10 control patients who underwent esophagectomy for esophageal cancer. Hematoxylin–eosin staining was performed to assess inflammation infiltration, fibrosis, and atrophy. Specific immunohistochemical staining was performed to identify ICCs and neuronal nitric oxide synthase (nNOS). RESULTS: The number of ICCs in patients with type I achalasia was significantly lower than that in patients with type II achalasia, followed by that in control patients (type I vs type II vs control group= 0.4 vs 1.2 vs 9.5; P < 0.001). The number of nNOS-positive cells was significantly lower in patients with achalasia than that in control patients (type I vs type II vs control group = 0.0 vs 0.0 vs 8.0; P < 0.001). Nonrecurrent group had significantly more ICCs than recurrent group (type I: nonrecurrent vs recurrent = 1.0 vs 0.1; P = 0.010; type II: nonrecurrent vs recurrent = 2.0 vs 0.4; P = 0.004). DISCUSSION: ICCs and nNOS-positive cells reduced significantly in LES muscle of patients with achalasia. The number of ICCs differed among different achalasia subtypes and was related to patients' clinical prognosis.

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Achalasia is a primary esophageal motility disorder manifested by dysphagia and chest pain that impair patients' quality of life, and it also leads to chronic esophageal inflammation by food retention and increases the risk of esophageal cancer. Although achalasia has long been reported, the epidemiology, diagnosis and treatment of achalasia are not fully understood. The current clinical dilemma of achalasia is mainly due to its unclear pathogenesis. In this paper, epidemiology, diagnosis treatment, as well as possible pathogenesis of achalasia will be reviewed and summarized. The proposed hypothesis on the pathogenesis of achalasia is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in lower esophageal sphincter.

Background Achalasia is a primary esophageal motility disorder with potential molecular pathogenesis remaining uncertain. This study aimed to identify the differentially expressed proteins and potential pathways among achalasia subtypes and controls to further reveal the molecular pathogenesis of achalasia. Methods Paired lower esophageal sphincter (LES) muscle and serum samples from 24 achalasia patients were collected. We also collected 10 normal serum samples from healthy controls and 10 normal LES muscle samples from esophageal cancer patients. The 4D label-free proteomic analysis was performed to identify the potential proteins and pathways involved in achalasia. Results Analysis of Similarities showed distinct proteomic patterns of serum and muscle samples between achalasia patients and controls (both P &lt; 0.05). Functional enrichment analysis suggested that these differentially expressed proteins were immunity-, infection-, inflammation-, and neurodegeneration-associated. The mfuzz analysis in LES specimens showed that proteins involved in the extracellular matrix–receptor interaction increased sequentially between the control group, type III, type II, and type I achalasia. Only 26 proteins altered in the same directions in serum and muscle samples. Conclusions This first 4D label-free proteomic study of achalasia indicated that there were specific protein alterations in both the serum and muscle of achalasia, involving immunity, inflammation, infection, and neurodegeneration pathways. Distinct protein clusters between types I, II, and III revealed the potential molecular pathways associated with different disease stages. Analysis of proteins changed in both muscle and serum samples highlighted the importance of further studies on LES muscle and revealed potential autoantibodies.

Objective In this systematic review and meta‐analysis we aimed to determine the efficacy and safety of magnetic sphincter augmentation (MSA) in the management of refractory gastroesophageal reflux disease (rGERD). Methods Literature search was conducted in PubMed, the Cochrane Library, EMBASE, Web of Science, OpenGrey and ClincalTrials.gov for single‐arm studies evaluating the efficacy and safety of MSA in rGERD or comparative studies with proton pump inhibitor (PPI) or laparoscopic Nissen fundoplication (LNF) serving as the control published until April 2020. Primary outcome was the rate of postoperative PPI use, and secondary outcomes included postoperative GERD‐health‐related quality of life (GERD‐HRQL), normalization of acid exposure time (AET) and incidence of procedure‐related adverse events (AE). Results Ten single‐arm studies, one randomized controlled trial and three cohort studies involving 1138 participants were included. Post‐MSA PPI withdrawal, significant GERD‐HRQL improvement and AET normalization were achieved in 87.0%, 88.0% and 75.0% of the patients, respectively. The incidence of postoperative dysphagia was 29% and endoscopic dilation was required in 7.4% of patients undergoing MSA. MSA showed a better efficacy in symptom control than PPI (PPI cessation: 91% vs 0%; GERD‐HRQL improvement: 81% vs 8%) and similar effectiveness but a lower risk of gas‐bloat syndrome (risk ratio [RR] 0.69, 95% confidence interval [CI] 0.51‐0.93, P = 0.01) and better reserved ability to belch (RR 1.48, 95% CI 0.76‐2.86, P = 0.25) compared with LNF. Conclusions MSA was an effective and safe therapy for rGERD. Well‐designed randomized trials that compare the efficacy of MSA with other therapies are needed.